Depression is a very common medical disorder that affects every 1 in 5 individual in the U.S. It is often said that depression results from chemical imbalance in the brain, either too little or too much of certain chemicals in the brain. Factors that lead to chemical imbalance could be one or a combination of recent events, past issues, genetic vulnerability, medications, medical problems etc.

Antidepressants, as the name suggests treat depressants. About 50% of people who take antidepressant find their depression symptoms halved. The first antidepressant drug was Imipramine (Tofranil). It was marketed in 1958. Today, there are close to 30 antidepressants that are grouped into five categories. Each has different chemical structures to treat moderate to severe depression.

Types of antidepressants

There are five main types of antidepressants. They differ in the neurotransmitters they affect.

1. Monoamine oxidase inhibitors (MAOIs)

2. Serotonin and norepinephrine reuptake inhibitors (SNRIs)

3. Selective Serotonin Reuptake Inhibitors (SSRIs)

4. Tricyclic antidepressants (TCAs)

5. Atypical antidepressants

Under these five types of antidepressants, there are around 30 antidepressant medicines. They are grouped based on how they work. Each antidepressant is different and affects different systems of the brain to different degrees. Considering the difference to be as small as 3-4%, it can have an enormous impact on an individual to alleviate depression symptoms.

Patients respond to antidepressants differently. Some may respond to or tolerate one antidepressant and not respond to or tolerate another antidepressant. Each antidepressant has different use, adverse effects and drug interactions. Prescription of anti-depressants is based on the symptoms, patient's age, family history, drug tolerance, side effects and past response to antidepressants.

Monoamine oxidase inhibitors (MAOIs)

How MAOIs work: When depressed, the brain chemistry is impacted. The level of three neurotransmitters, norepinephrine, serotonin and dopamine is low. Collectively, these three are called monoamines. An enzyme called monoamine oxidase is linked to removing the three neurotransmitters from the brain.

Antidepressants such as MAOIs inhibit monoamine oxidase and allow more of the three neurotransmitters to remain in the brain. The levels of the chemicals rise. This elevates mood as there is improved brain cell communication.

MAOIs have been replaced by antidepressants that are far safer and cause fewer side effects. MAOIs carry the risk of considerable side effects and drug interactions.

The Food and Drug Administration has approved these MAOIs to treat depression.

Isocarboxazid (Marplan)

Phenelzine (Nardil)

Selegiline (Emsam)

Tranylcypromine (Parnate)

Of the four, Selegiline (Emsam) is a skin patch approved to treat major depressive disorder. The other three are available as oral medications.

Side effects of MAOIs

MAOIs carry the risk of considerable side effects and drug interactions. Hence, MAOIs are prescribed when other depressants fail to provide desired results.

Common side effects of MAOIs are dry mouth, nausea, diarrhea or constipation, headache, drowsiness, tiredness, weakness, insomnia, dizziness or lightheadedness, skin reaction at the patch site.

When two or more drugs interact, it can reduce the efficacy of the drug. Possibility of unexpected side effects is high. Knowing drug interactions is critical for your health. It is best to discuss with health care provider before taking MAOI anti-depressant medication.

MAOIs can cause serious reactions if taken with certain other drugs.

MAOI interaction with other antidepressants

Tricyclic antidepressants

Tetracyclic antidepressants

SSRIs

Other MAOIs

Serotonin antagonists

Mirtazapine

Venlafaxine

MAOI interaction with asthma medicines

Ephedrine and other asthma drugs

Inhalants with albuterol, metaproterenol or other beta-adrenegic bronchodilators

Theophylline

MAOIs interact with cold, cough, allergy, sinus, decongestant and hay fever medications. The medicines can be in the form of tablets, ointment, sprays or drops.

MAOIs with certain foods and beverages can cause dangerous interactions. It is best to consult your doctor for a complete list of foods and beverages to be abstained from. Take for example tyramine, an amino acid which occurs naturally in the body and helps regulate blood pressure. When MAOI is recommended, foods and beverages with tyramine should be restricted as it can quickly reach dangerous levels and spike blood pressure.

MAOIs are prescribed only when all the other anti-depressants don't work. It's mainly due to the 'cheese effect'. The connection is established. Yes, those who ate products containing cheese while on an MAOI experienced severe headaches. Further, MAOI is not recommended for children or teenagers.

MAOI is given to people:

When other antidepressants haven't worked

Who cannot tolerate the side effects of other antidepressants

Who have a family or personal history of using MAOI successfully

With unusual depression symptoms

MAOI and psychotherapy

MAOI works best when paired with some form of psychotherapy. An antidepressant alone would not suffice to meet the behavioral, emotional or underlying mental health issues. A qualified psychotherapist can help in coping with the condition.

SNRIs type of anti-depressant

How SNRIs work: Serotonin and Norepinephrine Reuptake Inhibitors affect two important brain chemicals, serotonin and norepinephrine. Serotonin is regarded as a 'feel-good' chemical. It is associated with positive feelings of wellbeing. Norepinephrine is associated with alertness and energy. An imbalance can cause depression.

SNRIs block the reabsorption (recycling) of the neurotransmitters in the brain. Reabsorption is going back into the cells that released them. When reabsorption happens, the levels go down. When SNRIs block reabsorption, the levels of the two neurochemicals increase and helps improve and elevate mood, enhances the alertness of the person experiencing symptoms of depression.

This type of anti-depressant is also called dual reuptake inhibitors or dual-acting antidepressant as they affect two important brain chemicals-serotonin and norepinephrine. The Food and Drug Administration has approved these MAOIs to treat depression.

Desvenlafaxine (Pristiq, Khedezla)

Duloxetine (Cymbalta)

Levomilnacipran (Fetzima)

Venlafaxine (Effexor XR)

SNRIs interaction with other medications

Interactions between medicines can cause reactions which can be life-threatening. Before taking an anti-depressant, inform doctor of any/all medicines being taken. SNRIs interact with medicines like:

Warfarin (Coumadin, Marevan)

St.John's wort

MAOIs

Tricyclic antidepressants

Triptans

Anticoagulants

Antihistamines

Alcohol

Theophyline

Codeine

Beta blocker medications for heart disease or high blood pressure

Benzodiazepines

Cisapride

Carbamazepine (Tegretol)

Thioridazine (Mellaril)

Terfenadine (Seldane)

Sumatriptin for migraine headaches

Ketoconazole

Trimadol

Other antidepressants

Besides some medicines, intake of certain substances as given below, can increase the toxicity of SNRIs.

Alcohol

Drugs that depress the central nervous system

Decongestants

Medications used for insomnia

Side effects of SNRIs

Compared to other types of anti-depressants, SNRIs have fewer side effects. In most cases, the side effects go away after few days or weeks of taking SNRIs. Anti-depressant medications take four to six weeks to start working.

It is always best to inform the doctor of any side effect if experienced while taking any antidepressant. While taking an anti-depressant, it is not necessary for the patient to experience all the side effects. It may be any one or a few of these side effects.

Mild nausea

Headache

Diarrhea

Abdominal cramps

Pain related to abdominal cramps

Vomiting

Constipation

Dizziness

Dry mouth

Difficulty in sleeping

Excessive sweating

Sexual problems

Loss of appetite

Weight loss

Caution

Women who are pregnant or thinking of becoming pregnant and breastfeeding mothers should let the healthcare provider know while being prescribed an anti-depressant medication, including SNRIs.

Serotonin syndrome may occur when the levels of serotonin in the brain reaches high levels. It is triggered when an SNRI antidepressant is taken with another drug with high levels of serotonin (example – St.John's wort). Seek emergency medical help. The symptoms of severe serotonin level rise are very high fever, seizures, irregular heartbeat and unconsciousness.

Seek immediate medical attention, if while taking SNRIs, the patient:

1. Has abnormal bleeding

2. Has suicidal thoughts or behavior

3. Blood pressure levels rise (may increase when taking SNRIs)

4. Pressure of the fluid inside eye changes (narrow angle glaucoma)

Contraindication of SNRIs

Two SNRIs, namely Duloxetine and Milnacipran (approved to treat Fibromyalgia) is contraindicated in patients with uncontrolled narrow angle or angle-closure glaucoma. SNRIs can cause liver problems, including hepatitis. SNRIs are not recommended for people with liver problems and kidney problems (renal failure).

There is a high possibility of SNRIs affecting activities requiring mental or motor concentration. At least for the first few days or till such time the patient is accustomed to the effect, it is best to have family or friends or paid support.

Tricylic antidepressants (TCAs)

Also known as cyclic antidepressants or TCAs, this type of antidepressant is best suited for patients and is prescribed by doctor only when other drugs have failed to treat depression. TCAs are similar to SNRIs. TCAs increase levels of norepinephrine and serotonin, the two neurotransmitters and block the action of acetylcholine, another neurotransmitter. By restoring the balance in the brain Tricyclic antidepressants alleviate depression.

FDA approved Tricyclic antidepressants are:

Amitriptyline

Amoxapine

Desipramine (Norpramin)

Doxepin (Silenor)

Imipramine (Tofranil)

Nortriptyline (Pamelor)

Protriptyline (Vivactil)

Trimipramine (Surmontil)

Besides these, Maprotiline is a Tetracyclic antidepressant that is FDA approved to treat depression.

Side effects of Tricyclic antidepressants

40% of people taking antidepressants have side effects. Initially in most cases, the side effects may cause problem but would improve with time. Benefits of treatment outweigh the initial problems.

Tricyclic antidepressants are associated with many side effects. This is a reason why doctors prescribe other antidepressants with fewer side effects. Side effects are due to the interference of tricyclic antidepressants with autoimmune nervous system. Common side effects of TCAs are:

Dry mouth

Blurred vision

Constipation

Problems passing urine

Feeling drowsy

Feeling dizzy

Sudden weight gain or weight loss

Excessive sweating at night

Skin rash

Palpitation (Fast heart rhythm)

It is best to seek medical attention if the person experiences symptoms like:

Trouble breathing

Swelling of face, lips, tongue or throat

Hives

Thoughts of suicide

Agitation and restlessness

Seizures

Fast heartbeat

Nausea and vomiting

Drug interaction includes interaction of drugs with other drugs, interaction of drugs with food (drug-food interaction) and other substances. The interaction may increase or decrease the effectiveness of the drugs and/or its side effects. Sometimes, the interactions may lead to psychological sufferings.

Prior to starting treatment with any medication, including antidepressant, make a list of all the medications being taken and provide it to the health care provider.

MAOIs

Hypotensive agents (medicines used to treat blood pressure)

Central nervous system depressants like alcohol, sedatives or hypnotics and barbiturates

Anti psychotic agents

Cimetidine, SSRIs, SNRIs, levodopa, anticoagulants

Drugs that block acetylcholine

Clonidine

Sleeping pills

Pain killers

Tranquillizers

Antihypertensive medicines

Antihistamines

Antifungal medicines

Caution

While taking TCAs it is best not to drink alcohol, as it can add to the side effects. People who have seizures, difficulty urinating, glaucoma or heart conditions (coronary heart disease) the symptoms can get worse.

SSRIs or Selective serotonin reuptake inhibitors

Of the different types of antidepressants for depression, SSRIs or Selective Serotonin Reuptake Inhibitors are most commonly prescribed. SRIs are relatively safe and have fewer side effects.

SSRIs ease symptoms of moderate to severe depression by increasing the levels of serotonin in the brain. Serotonin is one of the chemicals (neurotransmitter) that help to relay messages from one area of the brain to another. Serotonin is believed to influence a variety of psychological and other body functions. An imbalance in serotonin levels may influence mood and lead to depression. Low brain cell production of serotonin, a lack of receptor sites to receive the serotonin that is made, inability of serotonin to reach the receptor sites, shortage of tryptophan – chemical from which serotonin is made, any of these can lead to depression.

SSRIs are designed to boost serotonin levels. This enables production of new brain cells which in turn allows the depression to ease. SSRIs are called selective as they primarily affect serotonin and not other transmitters. SSRIs approved by the FDA for the treatment of depression are:

Citalopram (Celexa)

Escitalopram (Lexapro)

Fluoxetine (Prozac)

Fluvoxamine (Luvox, Luvox CR)

Paroxetine (Paxil, Paxil CR)

Sertraline (Zoloft)

SSRIs and drug interaction

SSRIs are subject to extensive oxidative metabolism (a chemical process wherein oxygen is used to make energy from carbohydrates) in the liver. Drug interactions with SSRI are either due to overdosing of the drug combined.

Non-steroidal anti-inflammatory drugs (NSAIDs)

Anti platelets (to prevent blood clots)

Theophylline (to treat asthma)

Medicines to treat Schizophrenia and psychosis

Medicines to treat severe depression and bipolar disorder

Medicines to treat migraines

Decongestants

Other antidepressants

Foods or substances to avoid while taking SSRIs

Alcohol

Diuretics

St.John's wort

Caffeine (Excessive consumption)

Grape fruit

Cheese (before or after taking pills)

SSRIs are not suitable for people with certain medical conditions. While an antidepressant medication is being prescribed, the health care provider should be informed if the patient has any of these medical conditions to weigh the benefits vs. risks.

Bipolar disorder

Hemophilia (Bleeding disorder)

Type 1 diabetes or type 2 diabetes

Epilepsy

Narrow angle glaucoma

Serious kidney, liver or heart problems

Side effects of SSRIs

The object of knowing side effects of any medication is to be aware of what to expect and to work out a strategy to continue medication and speed up recovery. Though SSRIs are the most commonly prescribed antidepressant, their side effects cannot be ignored.

All SSRIs tend to work in a similar way. But the active ingredient differs. Some people may experience side effects and some people may not. And even if experienced, common side effects of SSRIs are most likely to improve after few doses once the body adjusts to the medication. Talk to health care provider to know possible ways of reducing these side effects. For example, taking medication with food can reduce risk of nausea.

Fatigue

Weight loss

Insomnia

Headaches

Nausea

Pupil dilation

Restlessness

Nervousness

Dizziness

Diminished sexual desire

Erectile dysfunction in men

Difficulty achieving orgasm (men and women)

Caution

There are risks associated with taking any type of antidepressants during pregnancy. The medication does cross the placenta and are found in both amniotic fluid and breast milk. Associated risks are preterm birth, low birth weight, birth defects and delays in developmental milestones. The health care provider would recommend use of antidepressant during pregnancy based on the balance between risks and benefits. SSRIs have the best safety record. To treat depression during pregnancy SSRIs like Citalopram (Celexa), Fluoxetine (Prozac) and Sertraline (Zoloft) are recommended by health care providers.

Atypical antidepressants

How it works: Typically, these antidepressants do not fit into other types of antidepressants. Each atypical antidepressant is unique and works in a different way to treat depression. Atypical antidepressants are recommended for patients with major depression with inadequate responses or intolerable side effects during first-line treatment with SSRIs.

The link between the three main monoamine neurotransmitters in the brain i.e. dopamine, norepinephrine and serotonin and depression symptom is certain. Increase or decrease of specific neurotransmitter brings about specific symptoms which in turn suggest that depression can be assigned to specific neurochemical mechanism. Accordingly, doctors prescribe specific antidepressant drug that target symptoms-specific neurotransmitters to treat patient.

Atypical antidepressants work in this manner by effecting changes in brain chemistry. They change the levels of one or more neurotransmitters, such as dopamine, serotonin or norepinephrine. Changing the balance of these chemicals help brain cells send and receive messages, which in turn boosts mood and provide a sense of relaxation.

Atypical antidepressants approved by the FDA to treat depression are:

Bupropion (Brand name:Wellbutrin, Forfivo XL, Aplenzin)

Mirtazapine (Brand name: Remeron)

Nefazodone

Trazodone

Vortioxetine (Brand name: Trintellix)

Side effects of atypical antidepressants

Some patients may not experience any side effect. Those who experience can feel assured that it may go away after a time. In case it persists, the health care provider may prescribe a different medication. Each atypical antidepressant is unique, side effects too vary.

Bupropion

Anxiety

Restlessness or agitation

Confusion

Constipation

Dry mouth

Headache

Insomnia

Increased and irregular heartbeat

Nausea

Sore throat

Tremor

Mirtazapine

Constipation

Dizziness or lightheadedness

Dry mouth

Increased appetite

Increased cholesterol

Increased or decreased blood pressure

Low white blood cell count

Sleepiness

Weakness

Weight gain

Nefazodone

Blurred vision

Confusion

Constipation

Dizziness or lightheadedness

Dry mouth

Headache

Low blood pressure

Nausea

Excessive sleep

Weakness

Trazodone

Excessive sleep

Headache

Dry mouth

Dizziness or lightheadedness

Nausea

Fatigue

Diarrhea

Constipation

Insomnia

Low blood pressure

Feeling confused

Blurred vision

Irregular heartbeat

Caution

Atypical antidepressants can cause some problems in some circumstances. While atypical antidepressant is prescribed for treatment of depression, the patient should inform the healthcare provider of any health issues and related medicines being taken.

Women who are pregnant or planning pregnancy should discuss the risks/benefits of taking atypical antidepressant. Never stop the medication suddenly and without informing the doctor as it poses great risks.

Seek immediate medical attention if symptoms related to Serotonin syndrome occurs. When two medications that affect an increase in serotonin are combined, it can lead to Serotonin Syndrome. Symptoms include anxiety, agitation, sweating, confusion, tremors, restlessness, lack of coordination and a rapid heartbeat.

Drinking alcohol or using illegal drugs while taking antidepressant medication may decrease the benefits, worsen the condition and increase adverse effects of the medication.

Atypical antidepressant Bupropion should be avoided by patients with seizure disorder or an eating disorder like bulimia or anorexia.

Mirtazapine is not approved for use in children. Also, Mirtazapine increases cholesterol levels.

Nefazodone can aggravate liver disease.

Trazodone is to be avoided by people with heart related ailments.

Vortioxetine is linked to risk of bleeding.

Atypical antidepressant - Drug and food interaction

Certain drugs or substances may increase blood levels and toxicity.

Bupropion

Alcohol

Drugs for insomnia

SSRIs

TCAs

MAOIs

Beta Blockers

Anti arrhythmic drugs

Levodopa

Duloxitine

Alcohol

Drugs for insomnia

Anti arrhythmic drugs

Phenothiazines

TCAs

MAOIs

Warfarin

Fluvoxamine

Fluoxetine

Paroxetine

Rdioquin

Quinolone antibiotics

Mirtazapine

drugs taken for insomnia

TCAs

Thyroid medication

Phenothiazines and Benzodiazepines

Nefazodone

Alcohol

Drugs for insomnia

Buspirone

Carbamazepine

Cisapride

Cyclosporine

Digoxin

Pimozide

Thioridazine

Triazolam

St.John's wort

SSRIs

TCAs

Drugs that lead to abnormal heart rhythms

Drugs to treat high cholesterol

Buspirone

Sibutramine

Sumatriptan

Drugs for migraine headache

Trazodone

Alcohol

Drugs taken for insomnia

Clonidine

Digoxin

MAOIs

Phenytoin

Warfarin

Antifungal agents

Carbamazepine

Phenothiazines

Ritonavir

SSRIs

St.John's wort

Drugs that cause abnormal heart rhythms

Venlafaxine

Clozapine

Desipramine

Haloperidol

Indinavir

SSRIs

Warfarin

Cimetidine

MAOIs

St.John's wort

Melancholic depression

Melancholic depression is a severe form of depressive disorder or mental illness and is psychotic in nature. It is primarily caused by biological and genetic factors rather than psychological factors. It is a mental state that is characterized by feelings of extreme sadness, hopelessness and loss of interest and pleasure in almost everything. Person with Melancholic depression becomes non-responsive to happy incidents or surroundings even for the short period. Melancholic depression also leads to psychomotor disturbances such as low energy, poor concentration, slowed or agitated movements.

Causes of melancholia

It is believed that certain biological factors and genetic factors play an important role in development of this clinical depression. Studies also show that those who suffer from melancholia generally have a family history of depression disorders. Melancholia may not be an outcome of few negative incidents in life, but surely such events act as a trigger and initiate the problem. Biologically, melancholic depression is believed to be caused by a chemical imbalance or malfunctioning of the neurotransmitters in the brain.

Symptoms of Melancholia

Little or no response to positive and pleasant events.

Total loss of interest in things.

Low moods in the morning hours associated with low energy levels.

Strong feeling of guilt without any apparent reason.

Psychomotor Retardation with lack of facial expressions, slowing down of speech and body movements. They may also exhibit Psychomotor agitation such as pacing, twirling the hair, gesturing extensively, speaking incoherently, or aggression.

A person is diagnosed as suffering from melancholia when constantly experiencing extreme sadness accompanied by any 3 or 4 features mentioned above.

Treatment options

Unlike situational depression which is caused by sad events in life, melancholia is caused by biological disorder. Hence counseling and psychotherapy is probably not the solution. Treatment requires physical intervention via antidepressant drugs and also Electroconvulsive therapy (ECT) or shock treatment in case of extreme severity. Electroconvulsive therapy is recommended only for the severest forms of depressions, when a patient is not responding to antidepressant treatment or is posing a threat to self or others. Electroconvulsive therapy has certain side effects like short and long-term memory loss, hence it is advised only when the situation demands.

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